Interferon patterns in cancer patients receiving CTLA-4 or PD-1/PD-L1 inhibitors versus autoimmune disease

Interferon Signature in Cancer Patients Treated With Anti-CTLA-4 and Anti-PD-1/PD-L1 Therapies: A Multicenter, Prospective, Observational Cohort Study Comparing Cancer Patients and Non-Cancer Patients With Systemic Autoimmune Diseases

This project will test whether blood interferon levels can help predict immune-related side effects in adults starting checkpoint inhibitor immunotherapy by comparing them with people who have autoimmune diseases.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital Universitario Araba (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, immunotherapy
• Locations: 1 site (Pamplona, Navarre)
• Trial ID: NCT07249060 on ClinicalTrials.gov

What this trial studies

This prospective observational study will enroll about 300 adults with cancer who are ICI‑naïve and about 40 adults with classified systemic autoimmune diseases to compare blood interferon (IFN) signatures. Small blood samples will be collected at predefined time points around initiation of anti‑CTLA‑4 and/or anti‑PD‑1/PD‑L1 therapy to measure IFN‑related biomarkers. Investigators will compare IFN patterns in cancer patients who do and do not develop immune‑related adverse events (irAEs) and contrast those patterns with IFN profiles from patients with lupus, Sjögren's, systemic sclerosis, or inflammatory myopathies. Patients on concurrent chemotherapy, tyrosine kinase inhibitors, high‑dose steroids, or with severe active autoimmune disease are excluded to isolate ICI effects.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) who are ICI‑naïve and about to start single or dual anti‑CTLA‑4 or anti‑PD‑1/PD‑L1 therapy, with expected survival over three months and not on significant immunosuppression.

Not a fit: Patients already receiving combination chemotherapy or targeted therapies, those on ongoing high‑dose immunosuppression, or with severe active autoimmune disease are excluded and would not be eligible to benefit from the study results.

Why it matters

Potential benefit: If successful, this work could allow clinicians to identify patients at higher risk of irAEs before symptoms appear and tailor monitoring or preventive measures.

How similar studies have performed: Previous research has linked interferon signatures to autoimmune disease and has shown exploratory associations with irAEs, but robust prospective validation as a predictive biomarker in this direct cancer versus autoimmune comparison remains limited.

Eligibility criteria

ICI cohort:

Inclusion Criteria:

* Initiation of treatment with a single ICI or dual ICI therapy in accordance with current clinical guidelines;
* Patients who are treatment-naïve to ICIs; and
* Age ≥18 years.

Exclusion Criteria:

* Estimated mortality of less than 3 months from the start of treatment;
* Current combination therapy with chemotherapy, tyrosine kinase inhibitors, or other tumor-specific treatments;
* Contraindication to treatment with ICIs (documented hypersensitivity, severe active autoimmune disease, Eastern Cooperative Oncology Group \[ECOG\] ≥3);
* Ongoing immunosuppressive therapy, including prednisone at doses \>10 mg/day or equivalent.

SAD cohort:

Inclusion Criteria:

* Meeting classification criteria for Systemic Lupus Erythematosus (SLE) (ACR/EULAR 2019), Primary Sjögren's Syndrome (pSS) (ACR/EULAR 2016), Systemic Sclerosis (SSc) (ACR/EULAR 2013), and/or Idiopathic Inflammatory Myopathy (IIM) (ACR/EULAR 2017).
* Age ≥18 years old.

Exclusion Criteria:

* Estimated mortality less than 3 months from the start of follow-up.
* Active immunosuppressive treatment, including prednisone at doses \>10 mg/day or equivalent.
* Recent diagnosis (\<1 year) of cancer, with the exception of non-melanoma skin cancer, or currently receiving active oncology-specific treatment.

Where this trial is running

Pamplona, Navarre

• Hospital Universitario de Navarra — Pamplona, Navarre, Spain (Recruiting)

Conditions Immune-Related Adverse Events; Lupus Erythematosus, Systemic; Sjogren Syndrome; Systemic Sclerosis; Inflammatory Myopathies; Solid Tumors; Immune Checkpoint Inhibitors; Adverse events